Translation repression by GLD-1 protects its mRNA targets from nonsense-mediated mRNA decay in C. elegans

Min Ho Lee, Tim Schedl

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Previously, we identified multiple in vivo mRNA targets of the maxi-KH/ STAR domain protein GLD-1 by their ability to interact with GLD-1 in cytoplasmic extracts and, for all targets tested thus far, GLD-1 functions as a translational repressor. However, here we show that GLD-1 stabilizes the mRNAs of two targets, gna-2 (T23G11.2) and Y75B12B.1. gna-2 mRNA has two upstream open reading frames (uORF), resulting in two premature stop codons. We found that gna-2 mRNA is a naturally occurring mRNA target of nonsense-mediated mRNA decay (NMD) and that the binding of GLD-1 protects gna-2 mRNA from NMD, likely by repressing translation of the uORFs. Therefore, gna-2 mRNA comes under two posttranscriptional controls: (1) translation regulation by a specific translational repressor, GLD-1; and (2) uORF elicited regulation, mainly through NMD. As a result, these two posttranscriptional controls together provide precise temporal and spatial control of gene expression. Consistent with this novel mode of regulation, when GLD-1 mRNA targets acquire premature stop codon mutations, GLD-1 protects them from NMD. Analysis of several mRNA targets containing premature stop codons suggests that in translation repression, GLD-1 either represses ribosome assembly on the target mRNA, or subsequent ribosome elongation to the premature stop codon.

Original languageEnglish
Pages (from-to)1047-1059
Number of pages13
JournalGenes and Development
Volume18
Issue number9
DOIs
StatePublished - May 1 2004

Keywords

  • Germ line
  • Nonsense-mediated mRNA decay
  • Translation repression
  • Upstream open reading frame
  • gld-1
  • gna-2

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